Field of the Invention and Description of the Prior Art
This invention is concerned with improvements in and relating to pharmaceutical compositions and, more particularly, is concerned with pharmaceutical compositions in dosage unit form encapsulated in soft gelatin capsules.
Pharmaceutical compositions in dosage unit form encapsulated in soft gelatin capsules (hereinafter simply referred to as "capsules") are well known and basically consist of a "fill", comprising one or more pharmaceutically active materials dissolved or dispersed in an appropriate liquid vehicle, encapsulated in a soft gelatin shell, generally comprising gelatin together with a plasticizer therefor such as glycerin.
On class of vehicle which has been proposed for use in the fill comprises the liquid polyethylene glycols, for example polyethylene glycols having a molecular weight from about 100 to 600. Certain pharmaceutically active ingredients, for example benzodiazepine type compounds such as temazepam and lormetazepam, have been shown to have improved bioavailability when administered as polyethylene glycol solutions in soft capsules.
However, the use of a liquid polyethylene glycol as a carrier vehicle has an attendant disadvantage in that the material is hygroscopic and tends to adsorb water from the shell and thereby embrittle it. This embrittlement may be enhanced by migration of the plasticizer from the shell into the fill. As a result of such embrittlement, which may take place over a matter of months or years, the shell loses its elasticity and, hence, its resistance to mechanical shocks which are, encountered in handling and transport of the capsules. In extreme cases the capsules may be sufficiently embrittled and/or suffer such mechanical shocks that a capsule is ruptured.
The problem is not so severe as to render capsules having a fill comprising a liquid polyethylene glycol vehicle useless. Many thousands, or indeed millions, of such capsules survive transport and handling without breakage. However, the problem does exist and is exacerbated by the fact that, since capsules are commonly packed together in several tens, hundreds or even thousands, one breaking, and therefore leaking, capsule can damage other capsules in the same package and thus render a large number of capsules useless.